Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China.
Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China.
Int Immunopharmacol. 2023 May;118:110031. doi: 10.1016/j.intimp.2023.110031. Epub 2023 Mar 16.
Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that causes pulmonary toxoplasmosis, although its pathogenesis is incompletely understood. There is no cure for toxoplasmosis. Coixol, a plant polyphenol extracted from coix seeds, has a variety of biological activities. However, the effects of coixol on T. gondii infection have not been clarified. In this study, we infected a mouse macrophage cell line (RAW 264.7) and BALB/c mice with the T. gondii RH strain to establish infection models in vitro and in vivo, respectively, to explore protective effects and potential mechanisms of coixol on lung injury caused by T. gondii infection. Anti-T. gondii effects and underlying anti-inflammatory mechanisms of coixol were investigated by real-time quantitative PCR, molecular docking, localized surface plasmon resonance, co-immunoprecipitation, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence microscopy. The results show that coixol inhibits T. gondii loads and T. gondii-derived heat shock protein 70 (T.g.HSP70) expression. Moreover, coixol reduced inflammatory cell recruitment and infiltration, and ameliorated pathological lung injury induced by T. gondii infection. Coixol can directly bind T.g.HSP70 or Toll-like receptor 4 (TLR4) to disrupt their interaction. Coixol prevented overexpression of inducible nitric oxide synthase, tumor necrosis factor-α, and high mobility group box 1 by inhibiting activation of the TLR4/nuclear factor (NF)-κB signaling pathway, consistent with effects of the TLR4 inhibitor CLI-095. These results indicate that coixol improves T. gondii infection-induced lung injury by interfering with T.g.HSP70-mediated TLR4/NF-κB signaling. Altogether, these findings suggest that coixol is a promising effective lead compound for the treatment of toxoplasmosis.
刚地弓形虫（Toxoplasma gondii）是一种专性细胞内寄生的原虫，可引起肺弓形虫病，但其发病机制尚不完全清楚。目前尚无针对弓形虫病的治愈方法。薏苡仁油是从薏苡仁种子中提取的一种植物多酚，具有多种生物学活性。然而，薏苡仁油对弓形虫感染的影响尚未阐明。在这项研究中，我们分别用弓形虫 RH 株感染小鼠巨噬细胞系（RAW 264.7）和 BALB/c 小鼠，建立了体外和体内感染模型，以探讨薏苡仁油对弓形虫感染引起的肺损伤的保护作用及其潜在机制。通过实时定量 PCR、分子对接、局部表面等离子体共振、共免疫沉淀、酶联免疫吸附试验、western blot 和免疫荧光显微镜观察，研究了薏苡仁油的抗弓形虫作用及其潜在的抗炎机制。结果表明，薏苡仁油抑制弓形虫负荷和弓形虫来源的热休克蛋白 70（T.g.HSP70）的表达。此外，薏苡仁油减少了炎性细胞的募集和浸润，并改善了弓形虫感染引起的肺部病理损伤。薏苡仁油可以直接与 T.g.HSP70 或 Toll 样受体 4（TLR4）结合，破坏它们的相互作用。薏苡仁油通过抑制 TLR4/核因子（NF）-κB 信号通路的激活，防止诱导型一氧化氮合酶、肿瘤坏死因子-α和高迁移率族蛋白 1 的过度表达，与 TLR4 抑制剂 CLI-095 的作用一致。这些结果表明，薏苡仁油通过干扰 T.g.HSP70 介导的 TLR4/NF-κB 信号通路，改善了弓形虫感染引起的肺损伤。总之，这些发现表明，薏苡仁油是一种有前途的治疗弓形虫病的有效先导化合物。
